Misleading results in studying pharmacodynamic interaction with oral anticoagulants

An experimental conditions is described in which the i.p. administration to rats of irritants produces a misleading increase of the anticoagulant effect of warfarin. Groups of 10 adult Wistar rats were treated i.p. or i.v. with HCl 0.1N plus warfarin p.o.; 24 hr after warfarin administration, prothrombin time was determined on citrate blood specimens and the animals were submitted to autopsy. When HCl is given i.p., a significant increase of prothrombin time is observed. On the contrary following i.v. administration no interference with the anticoagulant effect of warfarin is observed. Abdomen exploration of rats shows the presence of serum exudate following i.p. but not i.v. administration of HCl. The synergistic effect of i.p. administration of HCl on anticoagulant effect of warfarin appears an experimental artifact, probably attributable to a non-specific local irritating effect. This result stresses the need of caution in interpreting animal data indicating a synergism with oral anticoagulants.